Pregabalin Versus Levetiracetam In Partial Seizures

• ClinicalTrials.gov Identifier: NCT00537238
• Recruitment Status: Completed
• First Posted: October 1, 2007
• Results First Posted: July 11, 2013
• Last Update Posted: January 28, 2021
• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Information provided by (Responsible Party): Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )

Tracking Information

• First Submitted Date: September 27, 2007
• First Posted Date: October 1, 2007
• Results First Submitted Date: May 21, 2013
• Results First Posted Date: July 11, 2013
• Last Update Posted Date: January 28, 2021
• Study Start Date: October 2007
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 21, 2013)

Proportion of Participants With Response to Treatment [ Time Frame: Baseline up to Week 16 ]

Participants who had at least 50% reduction in 28-day seizure rate from baseline to the end of the maintenance phase were considered as responders. The 28-day seizure rate was calculated as number of partial seizures in the period divided by difference of number of days in the period and number of missing diary day entries in the period, multiplied by 28.

• Original Primary Outcome Measures (submitted: September 27, 2007): The primary outcome is efficacy - the responder rate, defined as the proportion of subjects who had at least a 50% reduction in 28 day seizure rate during the maintenance phase, as measured from baseline (data collected during 6 weeks).

Current Secondary Outcome Measures (submitted: May 21, 2013)

• Percent Change From Baseline in 28 Day Seizure Frequency at Week 16 [ Time Frame: Baseline, Week 16 ]
  The seizures were recorded by the participants, by a family member, by a caregiver, or by a legal guardian and documented in a daily seizure diary. Participant's 28-day seizure frequency of all partial seizure was assessed during double blind (TP + MP) phase compared with baseline.
• Change From Baseline in the Proportion of 28-day Secondarily Generalized Tonic-clonic (SGTC) Seizure Rate to 28-day All Partial Seizure Rate at Week 16 [ Time Frame: Baseline, Week 16 ]
  Change was calculated as (proportion of SGTC seizure rate divided by all partial seizure rates during double blind phase) minus (proportion of SGTC seizure rate divided by all partial seizure rates at baseline). Negative values indicated reductions in seizures.
• Percentage of Participants Without Seizures [ Time Frame: Baseline up to Week 16 ]
  Seizure free for 28 days was defined as participants who have not experienced any seizure (simple partial, complex partial and SGTC) for at least 28 consecutive days from their last seizure until the end of the maintenance phase. Same participant could be seizure free for a specific type of seizure but not necessarily for the other types of seizure.
• Change From Baseline in Brief Psychiatric Rating Scale - Anchored (BPRS-A) Total and Core Score at Week 7, 10, 13, 16 and Follow-up [ Time Frame: Baseline, Week 7, 10, 13, 16 and Follow-up (Day 7 of taper phase) ]
  BPRS-A:18-item clinician rated scale assesses somatic concern,anxiety, emotional withdrawal,conceptual disorganization,hallucinatory behavior(HB), guilt feelings,suspiciousness,disorientation,tension,mannerisms and posturing,grandiosity,depressive mood,hostility,motor retardation,uncooperativeness,unusual thought content,blunted affect,excitement. Items rated on 7-point scale 1 (not reported) to 7 (very severe). Total score=sum of items(range 18-126), core score=sum of conceptual disorganization, suspiciousness, HB, unusual thought content(range 4-28). Higher total/core score=more impairment.
• Hospital Anxiety and Depression Scale (HADS) Score [ Time Frame: Baseline, Week 16 ]
  HADS: participant rated questionnaire with 2 subscales. HADS-A assesses state of generalized anxiety (anxious mood, restlessness, anxious thoughts, panic attacks); HADS-D assesses state of lost interest and diminished pleasure response (lowering of hedonic tone). Each subscale comprised of 7 items with range 0 (no presence of anxiety or depression) to 3 (severe feeling of anxiety or depression). Total score 0 to 21 for each subscale; higher score indicates greater severity of anxiety and depression symptoms.
• Medical Outcomes Study Sleep Scale (MOS-SS) Score [ Time Frame: Baseline, Week 16 ]
  Participant-rated 12-item questionnaire to assess constructs of sleep over past week; 7 subscales:sleep disturbance,snoring,awakened short of breath,sleep adequacy,somnolence (range:0-100);sleep quantity (range:0-24),optimal sleep(yes/no), and 9 item index measures of sleep disturbance provide composite scores:sleep problem summary,overall sleep problem. Except adequacy,optimal sleep and quantity, higher scores=more impairment. Scores transformed (actual raw score[RS] minus lowest possible score divided by possible RS range*100);total score range:0-100;higher score=more intensity of attribute.
• Percentage of Participants With Optimal Sleep Assessed Using Medical Outcomes Study-Sleep Scale (MOS-SS) Score [ Time Frame: Baseline, Week 16 ]
  MOS-SS: participant-rated 12 item questionnaire to assess constructs of sleep over past week. It included 7 subscales: sleep disturbance, snoring, awakened short of breath, sleep adequacy, somnolence, sleep quantity and optimal sleep. Participants responded whether their sleep was optimal or not by choosing yes or no. Percentage of participants with optimal sleep are reported.

• Original Secondary Outcome Measures (submitted: September 27, 2007): Safety and tolerability - Change in seizure count frequency from baseline to endpoint, calculated as the percent change in 28 day seizure frequency during the maintenance phase of treatment compared with baseline.
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pregabalin Versus Levetiracetam In Partial Seizures
• Official Title: A Randomized, Double-Blind, Parallel-Group Multi-Center Comparative Flexible-Dose Study Of Pregabalin Versus Levetiracetam As Adjunctive Therapy To Reduce Seizure Frequency In Subjects With Partial Seizures
• Brief Summary: This study will compare pregabalin and levetiracetam in patients with partial seizures. It will also evaluate the safety and tolerability of pregabalin and levetiracetam in these patients.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Partial Seizures

Intervention

• Drug: pregabalin
  300, 450, 600 mg/day administered orally, BID until seizure control/improvement or intolerable side effects
• Drug: levetiracetam
  1000, 2000, 3000 mg/day administered orally, BID until seizure control/improvement or intolerable side effects

Study Arms

• Active Comparator: B
  Intervention: Drug: pregabalin
• Active Comparator: A
  Intervention: Drug: levetiracetam

• Publications *: Zaccara G, Almas M, Pitman V, Knapp L, Posner H. Efficacy and safety of pregabalin versus levetiracetam as adjunctive therapy in patients with partial seizures: a randomized, double-blind, noninferiority trial. Epilepsia. 2014 Jul;55(7):1048-57. doi: 10.1111/epi.12679. Epub 2014 Jun 5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 25, 2012): 509
• Original Enrollment (submitted: September 27, 2007): 400
• Actual Study Completion Date: May 2012
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects (male or female) must be > 18 years of age, with a diagnosis of epilepsy with partial seizures, as defined in the International League Against Epilepsy (ILAE) classification of seizures.
• Partial seizures may be simple or complex, with or without secondary tonic-clonic generalization.
• Subjects must be have been diagnosed with epilepsy for at least 2 years, and must have been unresponsive to treatment with at least two but no more than five prior antiepileptic drugs (AEDs), and at the time of study enrollment are on stable dosages of 1 or 2 standard AEDs.

Exclusion Criteria:

• Females who are pregnant, breastfeeding, or intend to become pregnant during the course of the trial will be excluded
• Subjects with other neurologic illness that could impair endpoint assessment, or subjects with Lennox-Gastaut syndrome, absence seizures, status epileptics within the 12 months prior to trial entry, or with seizures due to an underlying medical illness or metabolic syndrome, will be excluded.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Bulgaria, Colombia, Costa Rica, Czechia, France, Germany, Greece, India, Italy, Korea, Republic of, Lithuania, Mexico, Panama, Peru, Philippines, Russian Federation, Spain, Taiwan, Turkey, Venezuela
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT00537238
• Other Study ID Numbers: A0081157
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer ( Pfizer's Upjohn has merged with Mylan to form Viatris Inc. )
• Study Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: May 2013